New Stanford drug saves child with deadly genetic disease

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Zoe Harting, 4, was the first patient in the world to receive a breakthrough drug tested at Lucile Packard Children’s Hospital Stanford for infants born with spinal muscular atrophy, a rare genetic disease. (Provided photo)

At 7 months old, Zoe Harting got a shot at Lucile Packard Children’s Hospital Stanford that changed the course of her life.

A few months earlier, during a family Christmas vacation, Zoe’s parents, John and Eliza Harting of El Granada, realized something was wrong with their newborn.

Zoe was not developing at the same rate as her cousin even though the two were born just a week apart.

“Her cousin was very mobile: wriggling around, pushing stuff,” John Harting said. “Zoe wasn’t doing any of that. She was very quiet.”

The Hartings got the difficult news in early 2013 that Zoe had a deadly genetic disease: spinal muscular atrophy type 1, or SMA-1. Nationwide, about 250 babies are annually diagnosed with the rare disease, or about one in 10,000.

They learned that their first child was expected to die before she turns 2.

The Hartings were told there was nothing they could do. Distraught and frustrated, they joined an SMA support group, now called Cure SMA, and found a new pediatrician.

“It was a good thing we did,” John Harting said, “because our pediatrician happened to attend a conference where she met John Day.”

Dr. Day, director of the Neuromuscular Division and Clinics at Stanford University, was about to conduct a clinical trial using nusinersen as the first drug for SMA-1.

Zoe was the first baby in the world to receive the drug.

Day emphasized to the Hartings that he didn’t know if the treatment would work but they knew this was their only option.

In December 2016, the Food and Drug Administration approved Spinraza, developed by Biogen, as the first-ever sanctioned therapy for pediatric and adult patients with SMA.

Patients with SMA don’t produce enough of a protein called survival motor neuron, or SMN, which helps send signals from the spinal cord to muscles. When the muscles don’t get the signals, they atrophy.

Patients with SMA are missing the main gene, SMN1, that produces the protein. Patients have a second gene, SMN2, that also can produce the protein, but it only makes 5 to 10 percent of the amount needed.

The new drug works by acting like a patch to cover up the flawed portion of the SMN2 gene, which then spurs production of the protein.

“What we need to do is get a person up to about 50 percent of the normal amount of protein,” Day said. “It’s a 15-or-20 nucleic long signal that ends up being precisely paired with RNA. That’s what gives us this power. Make something incredibly focused on that flaw and it will fix that flaw but not have any other side effect.”

Day said it’s important that families now know there is something doctors can do if they see the infants early enough.

Day said there’s minimal awareness of the genetic disease — largely because many patients die so young — and pediatricians may not have updated information that treatment is available.

“Today, a pediatrician gets a genetic test back and they might very well tell the family, ‘Go home and love your child as long as you have them,’ ” Day said.

By the time a family does research and come across Day’s comprehensive care clinic, the child might be six or nine months old with irreversible muscular atrophy.

“If we see them early enough, before they see any symptoms, the child may not see any muscular impact,” Day said. “It’s potentially that effective of a treatment if we see the patient early enough.”

Day is an advocate for newborn genetic screening so SMA is identified at birth and treatment can begin before the child shows signs of the disease.

Babies are not yet being treated in utero, but such treatment is under development, Day said.

The Hartings shared their story this month as part of SMA Awareness Month, because they want families to know the importance of early detection and that there is treatment. About one in 50 parents are carriers of the recessive gene disorder.

Every four months, Zoe, who is now 4 years old, goes to Stanford for a 12 mg dose of the drug through a lumbar puncture, similar to an epidural. She gets physical therapy in between shots.

She has a weak musculature, and a simple cold can immobilize her. She can’t swallow or walk by herself. But after three years of treatment, she can now sit up, interact, draw and play. SMA does not affect cognitive development and there are small signs she will continue to gain muscle strength.

Day is quick to point out that the drug isn’t a magic wand that makes the disease go away. But he said Zoe, who had a “fairly aggressive course of SMA at three months,” has strength she didn’t have before treatment and there’s hope for continued improvement.

“She can talk, she can move her legs and arms, she even yells at me now,” Day said with a chuckle. “She has personality. She can throw a beach ball around. She’s going to have a life.”

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